Bayesian flux balance analysis applied to a skeletal muscle metabolic model

In this article, the steady state condition for the multi-compartment models for cellular metabolism is considered. The problem is to estimate the reaction and transport fluxes, as well as the concentrations in venous blood when the stoichiometry and bound constraints for the fluxes and the concentrations are given. The problem has been addressed previously by a number of authors, and optimization-based approaches as well as extreme pathway analysis have been proposed. These approaches are briefly discussed here. The main emphasis of this work is a Bayesian statistical approach to the flux balance analysis (FBA). We show how the bound constraints and optimality conditions such as maximizing the oxidative phosphorylation flux can be incorporated into the model in the Bayesian framework by proper construction of the prior densities. We propose an effective Markov chain Monte Carlo (MCMC) scheme to explore the posterior densities, and compare the results with those obtained via the previously studied linear programming (LP) approach. The proposed methodology, which is applied here to a two-compartment model for skeletal muscle metabolism, can be extended to more complex models.     

Encoding of vibrissal active touch

Mammals acquire much of their sensory information by actively moving their sensory organs. Yet, the principles of encoding by active sensing are not known. Here we investigated the encoding principles of active touch by rat whiskers (vibrissae). We induced artificial whisking in anesthetized rats and recorded from first-order neurons in the trigeminal ganglion. During active touch, first-order trigeminal neurons presented a rich repertoire of responses, which could not be inferred from their responses to passive deflection stimuli. Individual neurons encoded four specific events: whisking, contact with object, pressure against object, and detachment from object. Whisking-responsive neurons fired at specific deflection angles, reporting the actual whiskers' position with high precision. Touch-responsive neurons encoded the horizontal coordinate of objects' position by spike timing. These findings suggest two specific encoding-decoding schemes for horizontal object position in the vibrissal system.     

128 Some derivatives of 1,3-diazaadamantane strongly stimulate strand exchange reaction between short oligonucleotides

Earlier, we characterized the behavior of HG122 (compound III) in the DNA Strand Exchange Reaction (SER) and found that 1,3-diazaadamantane derivative facilitates SER in the system of short oligonucleotides (Gabrielian et al., 2011). In the present study, a series of new derivatives of 1,3-diazaadamantane have been synthesized with the purpose to discern how small variations in the compound structure can influence its activity in SER and try to get more effective substances for stimulation of SER. We revealed that most of the small variations in the structure significantly influenced the compounds’ efficacy in accelerating SER. For example, an increase in the compounds’ aliphatic chain lengths considerably enhanced its efficiency in SER stimulation and in the series of compounds presented in the Figure HG188 (compound IV) was eminently the most potent agent in the stimulation of SER. Small modifications in other parts of the 1,3-diazaadamantane molecule also influenced the SER stimulation and several derivatives more efficient in facilitating SER than HG122 were revealed. Some of the compounds exhibited virtually negligible capability to stimulate SER but, interestingly, out of 12 derivatives characterized, agents that retard spontaneous SER were not found. Earlier, the stimulation of the DNA strand exchange was documented for different ligands of the policationic nature such as Cationic Comb Copolymers (Kim et al., 2003), linker histones (Bocharova et al., 2012), cobalt hexamine (unpublished observation) etc. The present results provide us with a novel class of SER facilitating compounds – the cationic amphiphiles that can serve as interesting objects for further understanding of different aspects of DNA SER. Biomedical implications and prospects in biomedical applications of these and similar compounds’ activity in SER remain to be investigated.